Case Files Internal Medicine 4th Ed (2013)

FOURTH EDITION

CASE FILES

®

Internal Medicine
Eugene C. Toy, MD
The John S. Dunn, Senior Academic Chair and Program Director
The Methodist Hospital Ob/Gyn Residency Program
Houston, Texas
Vice Chair of Academic Affairs
Department of Obstetrics and Gynecology
The Methodist Hospital
Houston, Texas
Clinical Professor and Clerkship Director
Department of Obstetrics and Gynecology
University of Texas Medical School at Houston
Houston, Texas
Associate Clinical Professor
Weill Cornell College of Medicine
John T. Patlan Jr., MD
Associate Professor of Medicine
Department of General Internal Medicine
MD Anderson Cancer Center
Houston, Texas

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DEDICATION

To our coach Victor, and our father-son teammates Bob & Jackson, Steve
& Weston, Ron & Wesley, and Dan & Joel. At the inspirational JH Ranch

Father-Son Retreat, all of us, including my loving son Andy, arrived as
strangers, but in 6 days, we left as lifelong friends.
– ECT
To my parents who instilled an early love of learning and of the written word,
and who continue to serve as role models for life.
To my beautiful wife Elsa and children Sarah and Sean, for their patience and
understanding, as precious family time was devoted to the completion of
“the book.”
To all my teachers, particularly Drs. Carlos Pestaña, Robert Nolan, Herbert
Fred, and Cheves Smythe, who make the complex understandable, and who
have dedicated their lives to the education of physicians, and served as role
models of healers.
To the medical students and residents at the University of Texas-Houston Medical
School whose enthusiasm, curiosity, and pursuit of excellent and compassionate
care provide a constant source of stimulation, joy, and pride.
To all readers of this book everywhere in the hopes that it might help them to grow
in wisdom and understanding, and to provide better care for their patients who
look to them for comfort and relief of suffering.
And to the Creator of all things, Who is the source of all knowledge and healing
power, may this book serve as an instrument of His will.
– JTP


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CONTENTS

Reviewers / vii
Preface / ix

Acknowledgments / xi
Introduction / xiii
Section I
How to Approach Clinical Problems ........................................................................ 1
Part 1. Approach to the Patient. ............................................................................... 2
Part 2. Approach to Clinical Problem Solving ......................................................... 9
Part 3. Approach to Reading .................................................................................. 12
Section II
Clinical Cases .......................................................................................................... 17
Sixty Case Scenarios ............................................................................................... 19
Section III
Listing of Cases..................................................................................................... 521
Listing by Case Number ....................................................................................... 523
Listing by Disorder (Alphabetical) ....................................................................... 524
Index / 527


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REVIEWERS

Adam Banks
University of Texas – Houston Medical School
Class of 2012
~ez
Irving Basan
University of Texas – Houston Medical School
Class of 2012

Hubert M. Chodkiewicz
University of Texas – Houston Medical School
Class of 2012
Stephen Fisher
University of Texas – Houston Medical School
Class of 2012
Amber Gill
University of Texas – Houston Medical School
Class of 2012
Alicia Hernandez
University of Texas – Houston Medical School
Class of 2013
Matthew Hogue
University of Texas – Houston Medical School
Class of 2012
Michael Holmes
University of Texas – Houston Medical School
Class of 2012
Cassandra Kuchta
University of Texas – Houston Medical School
Class of 2013
Luke Martin
University of Texas – Houston Medical School
Class of 2012
Colin J. Massey
University of Texas – Houston Medical School
Class of 2012
Janice Wilson
University of Texas – Houston Medical School
Class of 2012

vii


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PREFACE

I have been deeply amazed and grateful to see how the Case Files® books have been
so well received, and have helped students to learn more effectively. In the 10 short
years since Case Files®: Internal Medicine has first made it in print, the series has
now multiplied to span the most of the clinical and the basic science disciplines,
and has been translated into over a dozen foreign languages. Numerous students
have sent encouraging remarks, suggestions, and recommendations, Three completely new cases have been written. Updated or new sections include health maintenance, nephritic syndrome, arthritis, diabetes, heart failure, and hyperlipidemia.
This fourth edition has been a collaborative work with my wonderful coauthors and
contributors, and with the suggestions from four generations of students. Truly, the
enthusiastic encouragement from students throughout not just the United States
but worldwide provides me the inspiration and energy to continue to write. It is thus
with humility that I offer my sincere thanks to students everywhere ... for without
students, how can a teacher teach?
Eugene C. Toy

ix


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ACKNOWLEDGMENTS

The curriculum that evolved into the ideas for this series was inspired by Philbert
Yau and Chuck Rosipal, two talented and forthright students, who have since
graduated from medical school. It has been a tremendous joy to work with my
excellent coauthors, especially Dr. John Patlan, who exemplifies the qualities of
the ideal physician—caring, empathetic, and avid teacher, and who is intellectually
unparalleled. Dr. Patlan would like to acknowledge several excellent medical students
from the University of Texas Medical School who thoughtfully reviewed many of
the cases and offered detailed advice on how to improve this book: Adam Banks,
Irving Basanez, Hubert Chodkiewicz, Stephen Fisher, Amber Gill, Matthew Hogue,
Michael Holmes, Luke Martin, Colin Massey, and Janice Wilson.
I am greatly indebted to my editor, Catherine Johnson, whose exuberance,
experience, and vision helped to shape this series. I appreciate McGraw-Hill’s
believing in the concept of teaching through clinical cases. I am also grateful to
Catherine Saggese for her excellent production expertise, and Cindy Yoo for her
wonderful editing. I cherish the ever-organized and precise Ridhi Mathur project
manager. It has been a privilege and honor to work with one of the brightest
medical students I have encountered, Molly Dudley who was the principal student
reviewer of this book. She enthusiastically provided feedback and helped to
emphasize the right material. I appreciate Linda Bergstrom for her sage advice and
support. At Methodist, I appreciate Drs. Judy Paukert, Dirk Sostman, Marc Boom,
and Alan Kaplan who have welcomed our residents; Debby Chambers, a brilliant
administrator and Linda Elliott, who holds the department together. Without my
dear colleagues, Drs. Konrad Harms, Priti Schachel, and Gizelle Brooks Carter,
this book could not have been written. Most of all, I appreciate my ever-loving
wife Terri, and our four wonderful children, Andy, Michael, Allison, and Christina,
for their patience and understanding.
Eugene C. Toy

xi

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INTRODUCTION

Mastering the cognitive knowledge within a field such as internal medicine is a
formidable task. It is even more difficult to draw on that knowledge, procure and
filter through the clinical and laboratory data, develop a differential diagnosis, and,
finally, to make a rational treatment plan. To gain these skills, the student learns best
at the bedside, guided and instructed by experienced teachers, and inspired toward
self-directed, diligent reading. Clearly, there is no replacement for education at the
bedside. Unfortunately, clinical situations usually do not encompass the breadth of
the specialty. Perhaps the best alternative is a carefully crafted patient case designed
to stimulate the clinical approach and the decision-making process. In an attempt to
achieve that goal, we have constructed a collection of clinical vignettes to teach
diagnostic or therapeutic approaches relevant to internal medicine.
Most importantly, the explanations for the cases emphasize the mechanisms and
underlying principles, rather than merely rote questions and answers. This book is
organized for versatility: it allows the student “in a rush” to go quickly through the
scenarios and check the corresponding answers, and it allows the student who wants
thought-provoking explanations to obtain them. The answers are arranged from simple
to complex: the bare answers, an analysis of the case, an approach to the pertinent
topic, a comprehension test at the end, clinical pearls for emphasis, and a list of references for further reading. The clinical vignettes are purposely placed in random order
to simulate the way that real patients present to the practitioner. A listing of cases is
included in Section III to aid the student who desires to test his/her knowledge of a
certain area, or to review a topic, including basic definitions. Finally, we intentionally
did not use a multiple choice question format in the case scenarios, because clues
(or distractions) are not available in the real world.

HOW TO GET THE MOST OUT OF THIS BOOK
Each case is designed to simulate a patient encounter with open-ended questions.
At times, the patient’s complaint is different from the most concerning issue, and
sometimes extraneous information is given. The answers are organized into four
different parts:

CLINICAL CASE FORMAT: PART I
1.

2.

Summary: The salient aspects of the case are identified, filtering out the extraneous information. Students should formulate their summary from the case before
looking at the answers. A comparison to the summation in the answer will help
to improve their ability to focus on the important data, while appropriately
discarding the irrelevant information—a fundamental skill in clinical problem
solving.
A Straightforward Answer is given to each open-ended question.

xiii


xiv

3.

INTRODUCTION

The Analysis of the Case is comprised of two parts:
a. Objectives of the Case: A listing of the two or three main principles that
are crucial for a practitioner to manage the patient. Again, the students are

challenged to make educated “guesses” about the objectives of the case upon
initial review of the case scenario, which helps to sharpen their clinical and
analytical skills.
b. Considerations: A discussion of the relevant points and brief approach to
the specific patient.

PART II
Approach to the Disease Process: It consists of two distinct parts:
a. Definitions: Terminology pertinent to the disease process.
b. Clinical Approach: A discussion of the approach to the clinical problem in
general, including tables, figures, and algorithms.

PART III
Comprehension Questions: Each case contains several multiple-choice questions,
which reinforce the material, or which introduce new and related concepts. Questions
about material not found in the text will have explanations in the answers.

PART IV
Clinical Pearls: Several clinically important points are reiterated as a summation of
the text. This allows for easy review, such as before an examination.


SECTION I

How to Approach
Clinical Problems
Part 1

Approach to the Patient

Part 2

Approach to Clinical Problem Solving

Part 3

Approach to Reading


2

CASE FILES: INTERNAL MEDICINE

Part 1. Approach to the Patient
The transition from the textbook or journal article to the clinical situation is one
of the most challenging tasks in medicine. Retention of information is difficult;
organization of the facts and recall of a myriad of data in precise application to
the patient is crucial. The purpose of this text is to facilitate in this process. The
first step is gathering information, also known as establishing the database. This
includes taking the history (asking questions), performing the physical examination, and obtaining selective laboratory and/or imaging tests. Of these, the historical
examination is the most important and useful. Sensitivity and respect should always
be exercised during the interview of patients.

CLINICAL PEARL
᭤

The history is the single most important tool in obtaining a diagnosis. All
physical findings and laboratory and imaging studies are first obtained and
then interpreted in the light of the pertinent history.

HISTORY
1. Basic information: Age, gender, and ethnicity must be recorded because some
conditions are more common at certain ages; for instance, pain on defecation
and rectal bleeding in a 20-year-old may indicate inflammatory bowel disease,
whereas the same symptoms in a 60-year-old would more likely suggest colon
cancer.
2. Chief complaint: What is it that brought the patient into the hospital or clinic?
Is it a scheduled appointment, or an unexpected symptom? The patient’s own
words should be used if possible, such as, “I feel like a ton of bricks are on my
chest.” The chief complaint, or real reason for seeking medical attention, may
not be the first subject the patient talks about (in fact, it may be the last thing),
particularly if the subject is embarrassing, such as a sexually transmitted disease,
or highly emotional, such as depression. It is often useful to clarify exactly what
the patient’s concern is, for example, they may fear their headaches represent an
underlying brain tumor.
3. History of present illness: This is the most crucial part of the entire database.
The questions one asks are guided by the differential diagnosis one begins to
consider the moment the patient identifies the chief complaint, as well as the
clinician’s knowledge of typical disease patterns and their natural history. The
duration and character of the primary complaint, associated symptoms, and
exacerbating/relieving factors should be recorded. Sometimes, the history will
be convoluted and lengthy, with multiple diagnostic or therapeutic interventions at different locations. For patients with chronic illnesses, obtaining prior
medical records is invaluable. For example, when extensive evaluation of a complicated medical problem has been done elsewhere, it is usually better to first


SECTION I: HOW TO APPROACH CLINICAL PROBLEMS

3

obtain those results than to repeat a “million-dollar workup.” When reviewing

prior records, it is often useful to review the primary data (eg, biopsy reports,
echocardiograms, serologic evaluations) rather than to rely upon a diagnostic
label applied by someone else, which then gets replicated in medical records and
by repetition, acquires the aura of truth, when it may not be fully supported by
data. Some patients will be poor historians because of dementia, confusion, or
language barriers; recognition of these situations and querying of family members is useful. When little or no history is available to guide a focused investigation, more extensive objective studies are often necessary to exclude potentially
serious diagnoses.
4. Past history:
a. Illness: Any illnesses such as hypertension, hepatitis, diabetes mellitus,
cancer, heart disease, pulmonary disease, and thyroid disease should be elicited. If an existing or prior diagnosis is not obvious, it is useful to ask exactly
how it was diagnosed; that is, what investigations were performed. Duration,
severity, and therapies should be included.
b. Hospitalization: Any hospitalizations and emergency room (ER) visits should
be listed with the reason(s) for admission, the intervention, and the location
of the hospital.
c. Blood transfusion: Transfusions with any blood products should be listed,
including any adverse reactions.
d. Surgeries: The year and type of surgery should be elucidated and any complications documented. The type of incision and any untoward effects of the
anesthesia or the surgery should be noted.
5. Allergies: Reactions to medications should be recorded, including severity and
temporal relationship to the medication. An adverse effect (such as nausea)
should be differentiated from a true allergic reaction.
6. Medications: Current and previous medications should be listed, including dosage, route, frequency, and duration of use. Prescription, over-the-counter, and
herbal medications are all relevant. Patients often forget their complete medication list; thus, asking each patient to bring in all their medications—both prescribed and nonprescribed—allows for a complete inventory.
7. Family history: Many conditions are inherited, or are predisposed in family members. The age and health of siblings, parents, grandparents, and others
can provide diagnostic clues. For instance, an individual with first-degree family members with early onset coronary heart disease is at risk for cardiovascular
disease.
8. Social history: This is one of the most important parts of the history in that the
patient’s functional status at home, social and economic circumstances, and goals
and aspirations for the future are often the critical determinant in what the best

way to manage a patient’s medical problem is. Living arrangements, economic
situations, and religious affiliations may provide important clues for puzzling diagnostic
cases, or suggest the acceptability of various diagnostic or therapeutic options. Marital


4

CASE FILES: INTERNAL MEDICINE

status and habits such as alcohol, tobacco, or illicit drug use may be relevant as risk
factors for disease.
9. Review of systems: A few questions about each major body system ensure that problems will not be overlooked. The clinician should avoid the mechanical “rapid-fire”
questioning technique that discourages patients from answering truthfully because of
fear of “annoying the doctor.”

PHYSICAL EXAMINATION
The physical examination begins as one is taking the history, by observing the patient and
beginning to consider a differential diagnosis. When performing the physical examination,
one focuses on body systems suggested by the differential diagnosis, and performs tests or
maneuvers with specific questions in mind; for example, does the patient with jaundice
have ascites? When the physical examination is performed with potential diagnoses and
expected physical findings in mind (“one sees what one looks for”), the utility of the
examination in adding to diagnostic yield is greatly increased, as opposed to an unfocused
“head-to-toe” physical.
1. General appearance: A great deal of information is gathered by observation, as
one notes the patient’s body habitus, state of grooming, nutritional status, level of
anxiety (or perhaps inappropriate indifference), degree of pain or comfort, mental
status, speech patterns, and use of language. This forms your impression of “who this
patient is.”
2. Vital signs: Vital signs like temperature, blood pressure, heart rate, respiratory rate,

height, and weight are often placed here. Blood pressure can sometimes be different in
the two arms; initially, it should be measured in both arms. In patients with suspected
hypovolemia, pulse and blood pressure should be taken in lying and standing positions
to look for orthostatic hypotension. It is quite useful to take the vital signs oneself,
rather than relying upon numbers gathered by ancillary personnel using automated
equipment, because important decisions regarding patient care are often made using
the vital signs as an important determining factor.
3. Head and neck examination: Facial or periorbital edema and pupillary responses
should be noted. Funduscopic examination provides a way to visualize the effects of
diseases such as diabetes on the microvasculature; papilledema can signify increased
intracranial pressure. Estimation of jugular venous pressure is very useful to estimate
volume status. The thyroid should be palpated for a goiter or nodule, and carotid
arteries auscultated for bruits. Cervical (common) and supraclavicular (pathologic)
nodes should be palpated.
4. Breast examination: Inspect for symmetry and for, skin or nipple retraction with the
patient’s hands on her hips (to accentuate the pectoral muscles) and also with
arms raised. With the patient sitting and supine, the breasts should then be
palpated systematically to assess for masses. The nipple should be assessed for
discharge, and the axillary and supraclavicular regions should be examined for
adenopathy.


SECTION I: HOW TO APPROACH CLINICAL PROBLEMS

5

5. Cardiac examination: The point of maximal impulse (PMI) should be ascertained for size and location, and the heart auscultated at the apex of the heart as
well as at the base. Heart sounds, murmurs, and clicks should be characterized.
Murmurs should be classified according to intensity, duration, timing in the
cardiac cycle, and changes with various maneuvers. Systolic murmurs are very

common and often physiologic; diastolic murmurs are uncommon and usually
pathologic.
6. Pulmonary examination: The lung fields should be examined systematically
and thoroughly. Wheezes, rales, rhonchi, and bronchial breath sounds should be
recorded. Percussion of the lung fields may be helpful in identifying the hyperresonance of tension pneumothorax, or the dullness of consolidated pneumonia
or a pleural effusion.
7. Abdominal examination: The abdomen should be inspected for scars, distension, or discoloration (such as the Grey Turner sign of discoloration at the flank
areas indicating intraabdominal or retroperitoneal hemorrhage). Auscultation
of bowel sounds to identify normal versus high-pitched and hyperactive versus
hypoactive. Percussion of the abdomen can be utilized to assess the size of
the liver and spleen, and to detect ascites by noting shifting dullness. Careful
palpation should begin initially away from the area of pain, involving one
hand on top of the other, to assess for masses, tenderness, and peritoneal signs.
Tenderness should be recorded on a scale (eg, 1-4 where 4 is the most severe
pain). Guarding, and whether it is voluntary or involuntary, should be noted.
8. Back and spine examination: The back should be assessed for symmetry, tenderness, and masses. The flank regions are particularly important to assess for
pain on percussion, which might indicate renal disease.
9. Genitalia:
a. Females: The pelvic examination should include an inspection of the external genitalia, and with the speculum, evaluation of the vagina and cervix.
A pap smear and/or cervical cultures may be obtained. A bimanual examination to assess the size, shape, and tenderness of the uterus and adnexa is
important.
b. Males: An inspection of the penis and testes is performed. Evaluation for
masses, tenderness, and lesions is important. Palpation for hernias in the
inguinal region with the patient coughing to increase intraabdominal pressure is useful.
10. Rectal examination: A digital rectal examination is generally performed for
those individuals with possible colorectal disease, or gastrointestinal bleeding.
Masses should be assessed, and stool for occult blood should be tested. In men,
the prostate gland can be assessed for enlargement and for nodules.
11. Extremities: An examination for joint effusions, tenderness, edema, and cyanosis may be helpful. Clubbing of the nails might indicate pulmonary diseases such
as lung cancer or chronic cyanotic heart disease.

6

CASE FILES: INTERNAL MEDICINE

12. Neurologic examination: Patients who present with neurologic complaints
usually require a thorough assessment, including the mental status, cranial
nerves, motor strength, sensation, and reflexes.
13. Skin examination: The skin should be carefully examined for evidence of pigmented lesions (melanoma), cyanosis, or rashes that may indicate systemic disease (malar rash of systemic lupus erythematosus).

LABORATORY AND IMAGING ASSESSMENT
1. Laboratory:
a. Complete blood count (CBC): To assess for anemia and thrombocytopenia.
b. Serum chemistry: Chemistry panel is most commonly used to evaluate renal
and liver function.
c. Lipid panel: Lipid panel is particularly relevant in cardiovascular diseases.
d. Urinalysis: Urinalysis is often referred to as a “liquid renal biopsy,” because
the presence of cells, casts, protein, or bacteria provides clues about underlying glomerular or tubular diseases.
e. Infection: Gram stain and culture of urine, sputum, and cerebrospinal fluid,
as well as blood cultures, are frequently useful to isolate the cause of infection.
2. Imaging procedures:
a. Chest radiography: Chest radiography is extremely useful in assessing cardiac size and contour, chamber enlargement, pulmonary vasculature and infiltrates, and the presence of pleural effusions.
b. Ultrasonographic examination: Ultrasonographic examination is useful for
identifying fluid-solid interfaces, and for characterizing masses as cystic, solid,
or complex. It is also very helpful in evaluating the biliary tree, kidney size,
and evidence of ureteral obstruction, and can be combined with Doppler flow
to identify deep venous thrombosis. Ultrasonography is noninvasive and has
no radiation risk, but cannot be used to penetrate through bone or air, and is
less useful in obese patients.

CLINICAL PEARL
᭤

Ultrasonography is helpful in evaluating the biliary tree, looking for
ureteral obstruction, and evaluating vascular structures, but has limited
utility in obese patients.

c. Computed tomography: Computed tomography (CT) is helpful in possible intracranial bleeding, abdominal and/or pelvic masses, and pulmonary
processes, and may help to delineate the lymph nodes and retroperitoneal
disorders. CT exposes the patient to radiation and requires the patient to be
immobilized during the procedure. Generally, CT requires administration of a
radiocontrast dye, which can be nephrotoxic.


SECTION I: HOW TO APPROACH CLINICAL PROBLEMS

7

d. Magnetic resonance imaging: Magnetic resonance imaging (MRI) identifies soft-tissue planes very well and provides the best imaging of the brain
parenchyma. When used with gadolinium contrast (which is not nephrotoxic),
MR angiography (MRA) is useful for delineating vascular structures. MRI does
not use radiation, but the powerful magnetic field prohibits its use in patients
with ferromagnetic metal in their bodies, for example, many prosthetic devices.
e. Cardiac procedures:
i. Echocardiography: Uses ultrasonography to delineate the cardiac size,
function, ejection fraction, and presence of valvular dysfunction.
ii. Angiography: Radiopaque dye is injected into various vessels, and radiographs or fluoroscopic images are used to determine the vascular occlusion, cardiac function, or valvular integrity.
iii. Stress treadmill tests: Individuals at risk for coronary heart disease are
monitored for blood pressure, heart rate, chest pain, and electrocardiogram (ECG) while increasing oxygen demands on the heart, such as running on a treadmill. Nuclear medicine imaging of the heart can be added

to increase the sensitivity and specificity of the test. Individuals who cannot run on the treadmill (such as those with severe arthritis) may be given
medications such as adenosine or dobutamine to “stress” the heart.

INTERPRETATION OF TEST RESULTS: USING PRETEST
PROBABILITY AND LIKELIHOOD RATIO
Because no test is 100% accurate, it is essential when ordering a test to have some
knowledge of the test’s characteristics, as well as how to apply the test results to an
individual patient’s clinical situation. Let us use the example of a patient with chest
pain. The first diagnostic concern of most patients and physicians regarding chest
pain is angina pectoris, that is, the pain of myocardial ischemia caused by coronary insufficiency. Distinguishing angina pectoris from other causes of chest pain
relies upon two important factors: the clinical history, and an understanding of how
to use objective testing. In making the diagnosis of angina pectoris, the clinician
must establish whether the pain satisfies the three criteria for typical anginal pain:
(1) retrosternal in location, (2) precipitated by exertion, and (3) relieved within
minutes by rest or nitroglycerin. Then, the clinician considers other factors, such
as patient age and other risk factors, to determine a pretest probability for angina
pectoris.
After a pretest probability is estimated by applying some combination of statistical data, epidemiology of the disease, and clinical experience, the next decision is whether and how to use an objective test. A test should only be ordered
if the results would change the posttest probability high enough or low enough
in either direction that it will affect the decision-making process. For example, a
21-year-old woman with chest pain that is not exertional and not relieved by rest
or nitroglycerin has a very low pretest probability of coronary artery disease, and
any positive results on a cardiac stress test are very likely to be false positive. Any test
result is unlikely to change her management; thus, the test should not be obtained.


8

CASE FILES: INTERNAL MEDICINE

Similarly, a 69-year-old diabetic smoker with a recent coronary angioplasty who now
has recurrent episodes of typical angina has a very high pretest probability that the
pain is a result of myocardial ischemia. One could argue that a negative cardiac stress
test is likely to be falsely negative, and that the clinician should proceed directly to
a coronary angiography to assess for a repeat angioplasty. Diagnostic tests, therefore,
are usually most useful for those patients in the midranges of pretest probabilities in
whom a positive or negative test will move the clinician past some decision threshold.
In the case of diagnosing a patient with atherosclerotic coronary artery disease
(CAD), one test that is frequently used is the exercise treadmill test. Patients are
monitored on an electrocardiogram, while they perform graded exercise on a treadmill. A positive test is the development of ST-segment depression during the test;
the greater the degree of ST depression, the more useful the test becomes in raising
the posttest probability of CAD. In the example illustrated by Figure I–1, if a patient
has a pretest probability of CAD of 50%, then the test result of 2 mm of ST-segment
depression raises the posttest probability to 90%.
99

95
1

90

2

80
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60
50
40
30
%

20

50
20
10
5
2
1

5
10
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%

30
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10
5

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80

2

90

1

95

Posttest
probability

Likelihood ratio:
Sensitivity
1 Ϫ Specificity

99
Pretest
probability

Figure I–1. Nomogram illustrating the relationship between pretest probability, posttest probability,
and likelihood ratio. (Reproduced with permission from Braunwald E, Fauci AS, Kasper KL, et al.
Harrison’s Principles of Internal Medicine. 16th ed. New York, NY: McGraw-Hill; 2005:10.)


SECTION I: HOW TO APPROACH CLINICAL PROBLEMS

9

If one knows the sensitivity and specificity of the test used, one can calculate
the likelihood ratio of the positive test as sensitivity/(1 - specificity). Posttest
probability is calculated by multiplying the positive likelihood ratio by the pretest
probability, or plotting the probabilities using a nomogram (see Figure I–1).
Thus, knowing something about the characteristics of the test you are employing,
and how to apply them to the patient at hand is essential in reaching a correct diagnosis and to avoid falling into the common trap of “positive test = disease” and “negative test = no disease.” Stated another way, tests do not make diagnoses; doctors do,

considering test results quantitatively in the context of their clinical assessment.

CLINICAL PEARL
᭤

If test result is positive,
Posttest Probability = Pretest Probability × Likelihood Ratio
Likelihood Ratio = Sensitivity/(1 – Specificity)

Part 2. Approach to Clinical Problem Solving
There are typically four distinct steps to the systematic solving of clinical problems:
1. Making the diagnosis
2. Assessing the severity of the disease (stage)
3. Rendering a treatment based on the stage of the disease
4. Following the patient’s response to the treatment

MAKING THE DIAGNOSIS
There are two ways to make a diagnosis. Experienced clinicians often make a diagnosis very quickly using pattern recognition, that is, the features of the patient’s
illness match a scenario the physician has seen before. If it does not fit a readily
recognized pattern, then one has to undertake several steps in diagnostic reasoning:
1. The first step is to gather information with a differential diagnosis in mind.
The clinician should start considering diagnostic possibilities with initial contact with the patient, which are continually refined as information is gathered.
Historical questions and physical examination tests and findings are all tailored
to the potential diagnoses one is considering. This is the principle that “you find
what you are looking for.” When one is trying to perform a thorough head-totoe examination, for instance, without looking for anything in particular, one is
much more likely to miss findings.
2. The next step is to try to move from subjective complaints or nonspecific
symptoms to focus on objective abnormalities in an effort to conceptualize the
patient’s objective problem with the greatest specificity one can achieve. For

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CASE FILES: INTERNAL MEDICINE

example, a patient may come to the physician complaining of pedal edema, a
relatively common and nonspecific finding. Laboratory testing may reveal that
the patient has renal failure, a more specific cause of the many causes of edema.
Examination of the urine may then reveal red blood cell casts, indicating glomerulonephritis, which is even more specific as the cause of the renal failure.
The patient’s problem, then, described with the greatest degree of specificity,
is glomerulonephritis. The clinician’s task at this point is to consider the differential diagnosis of glomerulonephritis rather than that of pedal edema.
3. The last step is to look for discriminating features of the patient’s illness. This
means the features of the illness, which by their presence or their absence narrow the differential diagnosis. This is often difficult for junior learners because it
requires a well-developed knowledge base of the typical features of disease, so the
diagnostician can judge how much weight to assign to the various clinical clues
present. For example, in the diagnosis of a patient with a fever and productive
cough, the finding by chest x-ray of bilateral apical infiltrates with cavitation is
highly discriminatory. There are few illnesses besides tuberculosis that are likely
to produce that radiographic pattern. A negatively predictive example is a patient
with exudative pharyngitis who also has rhinorrhea and cough. The presence of
these features makes the diagnosis of streptococcal infection unlikely as the cause of
the pharyngitis. Once the differential diagnosis has been constructed, the clinician
uses the presence of discriminating features, knowledge of patient risk factors, and
the epidemiology of diseases to decide which potential diagnoses are most likely.

CLINICAL PEARL
᭤

There are three steps in diagnostic reasoning:
1. Gathering information with a differential diagnosis in mind

2. Identifying the objective abnormalities with the greatest specificity
3. Looking for discriminating features to narrow the differential diagnosis

Once the most specific problem has been identified, and a differential diagnosis
of that problem is considered using discriminating features to order the possibilities,
the next step is to consider using diagnostic testing, such as laboratory, radiologic,
or pathologic data, to confirm the diagnosis. Quantitative reasoning in the use and
interpretation of tests was discussed in Part 1. Clinically, the timing and effort with
which one pursues a definitive diagnosis using objective data depend on several
factors: the potential gravity of the diagnosis in question, the clinical state of the
patient, the potential risks of diagnostic testing, and the potential benefits or harms
of empiric treatment. For example, if a young man is admitted to the hospital with
bilateral pulmonary nodules on chest x-ray, there are many possibilities including
metastatic malignancy, and aggressive pursuit of a diagnosis is necessary, perhaps
including a thoracotomy with an open-lung biopsy. The same radiographic findings
in an elderly bed-bound woman with advanced Alzheimer dementia who would not